Biphenyl-4-carboxylic acid (R)-(6-(1-((4-fluorobenzyl)methylamino)ethylideneamino)-2(R)-hydroxyindan-1-yl)amide is described in PCT Publication Number WO 03/027061, published Apr. 3, 2003. The forms of the compound described in the above patent application are an anhydrous form and the acetonitrile solvate.
The present invention provides crystalline biphenyl-4-carboxylic acid (R)-(6-(1-((4-fluorobenzyl)methylamino)ethylideneamino)-2(R)-hydroxyindan-1-yl)amide hemihydrate, compositions thereof, methods of using the same, and processes for making the same. The crystalline hemihydrate of the present invention is useful as a selective agonist of the muscarinic M-1 receptor and, as such, is useful for treating a variety of disorders of the central nervous system and other body systems. These disorders include cognitive disorders, ADHD, obesity, Alzheimer's disease, psychoses including schizophrenia, and for alleviation of intraocular pressure such as that found in glaucoma. Because biphenyl-4-carboxylic acid (R)-(6-(1-((4-fluorobenzyl)methylamino)ethylideneamino)-2(R)-hydroxyindan-1-yl)amide is useful for treating disorders associated with muscarinic receptors, there is a need to produce it as a pure, stable, and crystalline form in order to fulfill exacting pharmaceutical requirements and specifications. The novel crystalline hemihydrate of this invention has suitable properties to be conveniently formulated on a commercial scale in, for example, tablets for oral administration, and has suitable processing and storage properties. In particular, the present crystalline hemihydrate is a form that is easy to make in a reproducible and consistent manner. Furthermore, the novel crystalline hemihydrate of this invention exhibits greater thermodynamic stability.
It has been surprisingly discovered that biphenyl-4-carboxylic acid (R)-(6-(1-((4-fluorobenzyl)methylamino)ethylideneamino)-2(R)-hydroxyindan-1-yl)amide can be prepared in a hemihydrate form and having advantageous properties and the manufacturing process for the new form fulfills the desirable features described above.